Program Project Abstract. Biomarkers of Exposure to Hazardous Substances Although our ability to analyze hazardous material in waste sites has improved dramatically in recent years, we are very limited in our ability to trace the movement of hazardous materials from Superfund sites through various media or to prioritize and mitigate the hazards involved. Our ability to predict exposure or effect of these materials on humans and their environment is still more limited. This Program consists of 8 integrated projects, 3 research support cores, a training core, a research translation core and an administrative core to address these problems. We will determine the "ate and transport of hazardous materials in ground water, surface water, and air as they move from toxic waste sites using classical and innovative methodologies. We will examine the effect of some of these materials using an pidemiological approach. Concurrently we will develop sensitive systems for evaluating the exposure and effect of populations to these materials. Immunochemical, cell based and other systems will be used to detect biomarkers. Development of these biomarkers will be based on a fundamental understanding of the toxicological processes involved. The project will emphasize multiple organsystems with an in vivo emphasis on pulmonary and reproductive effects. We also will explore new technologies for thermal and bioremediation of toxic waste and address possible lealth risks associated with these technologies. Rapid immunochemical and cell based analysis will supplement classical technologies for the evaluation of sites, validating models of transport from these sites, as well as determining luman susceptibility, exposure and effect. Modern mass spectral technology will be evaluated for monitoring parent lazardous chemicals as well as biomarkers of exposure and effect. We are expanding the use of transcriptomics, aroteomics, metabolomics and integrated bio informatics technologies to discover new mechanisms of action of lazardous materials and biomarkers for their action. The biomarkers developed in this project will serve as biological dosimeters in epidemiological and ecological studies in this and sister projects. The technologies developed in the project will be tested at field sites and transferred to end users through a research translation core.